Nearly half the people with AIDS who take the drug AZT for three years can be expected to develop an aggressive cancer called non-Hodgkin's lymphoma, according to an estimate derived from a new study by the National Cancer Institute of long-term recipients of the drug.
Of a sample of people who have been on AZT for just two years, 14 percent have already come down with lymphoma, the study found.
Non-Hodgkin's lymphoma is a tumor that was already known to develop often in people with weakened immune systems. It was recognized as a complication of acquired immune deficiency syndrome before AZT became widely used to treat the disease, but AIDS experts say that it has recently become much more common.
The report, published in today's issue of the Annals of Internal Medicine, said such tumors "may well become a limiting factor in the survival of patients with HIV infection" as new weapons are developed to keep the virus in check.
There is no direct evidence yet that AZT causes lymphoma. Rather, researchers said yesterday, AZT is probably contributing to the cancer's increasing frequency by allowing more AIDS patients to live longer with weakened immune systems, so that there is more time for the tumors to appear. But, they cautioned, further study could show that AZT promotes the cancer's development.
"Whatever is going on, it's certainly not as simple as: AZT causes lymphomas," said Paul Volberding, head of the AIDS program at San Francisco General Hospital. "What a number of us would speculate is that the risk of lymphomas increases the longer a person is infected with HIV," the human immunodeficiency virus, which causes AIDS.
In the new study, NCI researchers tracked 55 patients with AIDS or a related disorder called AIDS-related complex who were among the first long-term recipients of AZT. The patients participated in government studies conducted between 1985 and 1987. Eight patients, or 14.5 percent, developed non-Hodgkin's lymphomas after being treated with the drug for an average of 24 months.
Of the other patients, 29 died of other AIDS-related causes, 15 were alive and had not developed lymphomas, and three could not be located.
Using a standard statistical method to extrapolate from their findings, the researchers calculated that, for AIDS patients who survive for three years after starting to take AZT, the probability of developing non-Hodgkin's lymphoma is about 46 percent. Because that estimate was based on a small number of patients, the researchers said the estimate could be off. The true frequency could be as low as 20 percent or as high as 76 percent.
AZT, also called zidovudine and sold under the brand name Retrovir, is the only drug approved by the Food and Drug Administration for the treatment of HIV infection. Because it interferes with a cell's ability to make DNA, the chemical of which genes are made, researchers have long cautioned that long-term use might predispose patients to developing cancer. Cancer is known to result from mutations or other errors in DNA replication.
But despite that theoretical concern, AZT is the only antiviral drug that has been found to improve the survival of people with AIDS. Because it also slows progression of the disease in those infected with the virus, AZT is recommended for all HIV-infected people whose counts of specialized white blood cells called T4 cells have fallen below 500 per cubic millimeter of blood. The Centers for Disease Control estimates that about 1 million Americans are infected with the virus.
The new findings do not alter the current recommendations. Because patients in the study had extremely low T4 cell counts for many months, the conclusions may not be applicable to HIV-infected patients who go on AZT with higher T4 cell counts. This is because the immune system destroys new cancer cells before they can make tumors. Patients who start AZT with stronger immune systems may retain their natural cancer-fighting abilities.
Samuel Broder, director of the National Cancer Institute and the report's senior author, said he thought the lymphomas are occurring more often because patients are surviving for years with severely damaged immune systems, not because of AZT treatment. He noted that in other studies, lymphomas have been seen in AIDS patients who received other drugs or who received a placebo.
"In virtually any condition, whether acquired or genetically determined, where the immune system is severely damaged, the risk of lymphomas goes up," he said. "This is not something that caught everybody by surprise."